Plicatic acid esters

ABSTRACT

New compositions of matter comprising alkyl and aryl esters of plicatic acid, and the use of these esters as antioxidants for fats and oils, are disclosed.

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States aten [191 Howard et al.

[451 Aug. 28, 1973 PLICATIC ACID ESTERS Inventors: John Howard; Terence D. McIntosh,

' both of 0/0 Rayonier Incorporated,

Olympic Research Division, Shelton,

Wash. 98584 Filed: Aug. 13, 1972 Appl. No.: 171,753

Related US. Application Data Division of Ser. No. 710,775, March 6, 1968, which is a continuation-in-part of Ser. No. 687,092, Dec. l, 1967.

US. Cl. 99/163, 260/473 F, 252/404 Int. Cl A23d 5/04 Field of Search 99/163; 252/404,

Primary ExaminerNorman Yudkoff Assistant Examiner--Hiram H. Bernstein Attorney-James B. Raden [57] ABSTRACT New compositions of matter comprising alkyl and aryl esters of plicatic acid, and the use of these esters as antioxidants for fats and oils, are disclosed.

6 Claims, No Drawings PLICATIC ACID ESTERS This is a division of application Ser. No. 710,775 filed March 6, 1968, which is a continuation-in-part of our co-pending United States Patent application Ser. No. 687,092, filed Dec. 1, 1967, entitled Pure Crystalline Plicatic Acid Tetrahydrate and the Process for Making Same.

BACKGROUND OF THE INVENTION Plicatic acid has the following structure as shown by its chemical degradation products and X-ray crystallography in investigations by Gardner, Barton and Mac Lean, Can. J. Chem. 37, 1703-9 (1959); Gardner, MacDonald and MacLean, Can. J. Chem. 38, 2387-94 (1960) and Gardner, Swan, Sutherland and MacLean, Can. J. Chem. 44, 52-8 (1966).

n H on W10 o-cinon l $4100 CHQO CH A process for the separation and recovery of plicatic acid from the aqueous extract of western rod cedar is described in U.S. Pat. application Ser. No. 386,429 by D.W. Langille and Kenneth R. Gray, filed July 30, 1964, and a process for preparing pure crystalline plicatic acid tetrahydrate is described in our co-pending U.S. Pat. application Ser. No. 687,092, filed Dec. 1, 1967.

Plicatic acid-is known to be a safe and effective antioxidant for edible fats and oils. Moreover, the availability of very pure crystalline plicatic acid tetrahydrate has made possible the preparation of other pure derivitives of plicatic acid of interest to manufacturers of pharmaceuticals, food antioxidants, and similar products where maximum purity, stability and reproducibility are of importance. One line of such derivitives is the esters of plicatic acid which comprise the subject matter of the present invention.

SUMMARY OF THE INVENTION After an extensive investigation of possible procedures for preparing the esters'of placatic acid, we have prepared a large number of alkyl and aryl plicatates in crystalline and amorphous form, and we have determined the essential chemical and physical characteristics of these new compositions of matter. These esters where R is an alkyl radical containing from one to 18 carbon atoms or an aralkyl radical containing seven carbon atoms. Moreover, we have found, after extensive tests, that all of these alkyl and aralkyl plicatates have excellent antioxidant activity for edible fats and oils.

DETAILED DESCRIPTION The alkyl and aralkyl plicatates of our invention have i been prepared by one or more of the following methods: l) the direct esterificarion of pure plicatic acid tetrahydrate with the appropriate alkyl alcohol in the presence of an acid catalyst: (2) the direct esterification of crude red cedar extracts with methyl alcohol in the presence of an acid catalyst: (3) the replacement of the methyl group in methyl plicatate with a higher alkyl group by heating with a higher alcohol in the presence of an acid catalyst; (4) the acid catalyzed alcoholysis of plicatin (the lactone of plicatic acid) with an appropriate alkyl alcohol; and (5) the reaction of potassium plicatate with an appropriate alkyl or aralkyl halide. A large number of plicatic acid esters have been prepared by'the foregoing methods and the antioxidant properties of these esters have been confirmed.

The following examples are illustrative but not limitative of the preparation of the plicatic acid esters of our invention.

Example 1-Crystalline Methyl Plicatate Crystalline plicatic acid tetrahydrate (4.94 g., IOmM) was dissolved in 25 ml. of methanol containing 2.0 ml. of concentrated sulfuric acid. The mixture was then seeded and set aside at room temperature in a stoppered flask for 4 days. During this time the white crystals which had deposited were removed by filtration, washed free of sulfuric acid, dried under high vacuum at 10 0 C. and found to weigh 3.7 g. (85 percent yield). The melting point was 227-30C with some decomposition (Leitz hot stage apparatus). Analysis calculated for methyl plicate, C,,H,,0,,,:C, 57.79%; H, 5.54%; OCH 21.3%. Found: C, 57.58%; H, 5.54%; OCl'l 21.0%. The infra red spectrum in mineral oil showed a characteristic ester band at 1,735 cm. The ester was optically active [a] 67.6 (C, SDMF). Methyl plicatate was found to be practically insoluble in water, methanol, acetone, ethyl acetate, chloroform and hydrocarbons. The only solvents in which it was found to dissolve were dimethylformamide, dimethylacetamide and dimethylsulphoxide.

Example 2Crystalline Methyl Plicatate A solution of 4 g. of plicatin (the lactone of plicatic acid) (IOmM) in 15 ml. of methanol containing 0.2 ml. of concentrated sulfuric acid was gently refluxed with stirring. Within 10 minutes crystalline methyl plicatate began to separate from the reaction mixture. After 4 hours the reaction mixture was cooled and the product separated and washed with a little methanol. After drying 3.5 g. of pure white material melting at 227-30C. was obtained, percent yield). This material was identical to methyl plicatate prepared in Example 1. Example 3-Crystalline Ethyl Plicatate Crystalline plicatic acid tetrahydrate (4.94 g., IOmM) was dissolved in 25 ml. of denatured ethanol (Fisher Scientific Company) containing 2 ml. of con- 'centrated sulfuric acid. The solution was allowed to stand at room temperature in a stoppered flask for l month after which the white crystalline product was removed by filtration washed using alcohol and dried at 100C. under high vacuum. The yield was 3.32g or 76 percent. Melting point 2l4-16C with some decomposition. The analysis calculated for ethyl plicatate c n o c, 58.66%; H, 5.82%. Found: C, 58.75%; H, 5.83%. The compound was optically active, [a],,"+77.2 (C, DMF) and the infra red spectrum in mineral oil showed a characteristic ester band at 1,735 cm". The product was essentially insoluble in water, methanol, ethanol, acetone, ether and hydrocarbon solvents, moderately soluble in dioxane and very soluble in dimethyl formamide, dimethyl acetamide and dimethyl sulphoxide. Example 4Crystalline n-Propyl Plicatate In a similar manner to that described for methyl plicatate in Example 1 crystalline n-propyl plicatate was isolated in 57 percent yield. The white product melted at 186-8C. with some decomposition and analysized correctly for n-propyl plicatate. It was optically active, [01],, 75.8 (C, SDMF) and was found to be insoluble in water, but soluble in polar oganic solvents such as methanol, dioxane, dimethyl formamide, slightly soluble in ether, ethyl acetate and chloroform and insoluble in hydrocarbon solvents. Example 5 Crystalline iso-Propyl Plidatate In a similar manner to that described for methyl plicatate in Example 1 crystalline iso-propyl plicatate was isolated in 63 percent yield. The white product melted at l80-4C. with some decomposition and analyzed correctly for iso-propyl plicatate. The compound was optically active [a]27D +73.4 (C, 5 DMF) and showed similar solubility characteristics to the n-propyl ester described in Exampe 5. Example 6-2-Butyl Plicatate Crystalline potassium plicatate (40 g., 87mM) was dissolved in 200 ml. water and passed through a column of an ion exchange resin for a period of 2 hours. After washing residual plicatic acid from the column using 70 ml. water the eluant and washings were concentrated to a thick pale brown syrup whose weight was 46.9 g. indicating a residual amount of water still present. After dissolution of the syrupy plicatic acid in 200 ml. of Z-butanol and 50ml. of benzene containing 2 g. of p-toluene sulfonic acid, the mixture was refluxed for a period of 4 hours. The reaction mixture was then cooled and washed with 50 ml. of water containing 4 g. sodium acetate whereupon a stubborn emulsion formed. Filtration through celite followed by addition of 25 ml. of saturated brine resulted in a slow breakdown of the emulsion and effective separation of the phases. The organic phase was then dried overnight using sodium sulfate, filtered and evaporated down under vacuo to leave 45.8 g. of dark thick syrup. The infra red spectrum showed a strong absorption at 1,720 cm for the ester carbonyl with a very weak absorption shoulder at 1,785 cm for the lactone. The hydroxyl and aromatic functions absorbed at 3,450 cm and 1,615 cm respectively. Analysis calculated for C H O, C, 60.25%; H, 6.32%. Found: C, 59.2%; H, 63.3%. Example 7-Amorphous n-Hexyl Plicatate A stirred suspension of 4 g. of plicatin l0mM) in a solution of 2 g. n-hexyl alcohol (mM) in 15 ml. ethanol free chloroform containing 0.4 g. of concentrated sulfuric acid was refluxed for a total of 30 minutes.

During this time all the plicatin dissolved. The reaction mixture after cooling was treated with 50 ml. of Skellysolve B whereupon the white solid that precipitated was removed by filtration and washed with a further 50 ml. of Skellysolve B. The product was then dissolved in 50 ml. of dichloromethane containing 2 m1. of methanol and washed with 50 ml. of 2 percent sodium ace tate, 25 ml. of water and finally dried over magnesium sulfate. Removal of the magnesium sulfate and dichloromethane and final drying under high vacuum left 3 g. of white amorphous solid (59 percent yield). The compound was found to be homogeneous on a thin layer chromatogram using silica gel and -benzene:acetone:acetic acid 10:l0:1 as solvent system and iodine vapor developer. Analyses calculated for n-hexyl plicatate C H O C, 61.55%; H, 6.77%; OCH 12.25%. Found: C, 61.99%; H, 7.30%; OCH 12.3%. The infra red spectrum in mineral oil showed a characteristic ester band at 1,735 cm. The compound was very soluble in polar organic solvents such as methanol, acetone, ethyl acetate etc. and fairly soluble in chloroform, benzene and ether while insoluble in hydrocarbon solvents. Example 8Amorph0us l-Dodecyl Plicatate A stirred suspension of 4 g. of plicatin (l0mM) in a solution of 3.72 g. of l-dodecyl alcohol (20mM) in 15 ml. of ethanol free chloroform containing 0.4 g. of concentrated sulfuric acid was gently refluxed for a period of minutes. During this time all the plicatin had dissolved and been converted to ester. After cooling, the solution was washed with dilute brine, the chloroform phase dried over magnesium sulfate, filtered and treated with Skellysolve B to precipitate the ester as a thick syrup. Removal of the supernatant liquor by decantation and trituration of the syrup with more Skellysolve B followed by drying under high vacuum left a powdery amorphous product. Wt. 3.8g. Further purification was effected by dissolution in hot benzene followed by addition of Skellysolve B to precipitate a white product. This was found to be homogeneous on a thin layer chromatogram using benzene:acetone:acetic acid 10:10:1 as solvent system and iodine as developer. The product showed a characteristic ester absorption at 1,735 cm in the infra red. It showed solubility in polar organic solvents but was insoluble in hydrocarbon solvents. Example 9Amorphous l-Octadecyl Plicatate This compound was prepared in a similar manner to that described for l-dodecyl plicatate in Example 8 above. The formation of emulsions during washing was however very troublesome and resulted in a less pure product as judged by thin layer chromatography. Example 10- Crystalline Benzyl Plicatate A solution of 4.60 g. of crystalline potassium plicatate hemihydrate (9.8mM) in 15 ml. of dimethyl formamide containing 1.28 g. of benzyl chloride was heated to C. in a stoppered flask for a period of 45 minutes. After cooling, 50 ml. of water was added and the mixture washed free of any unreacted benzyl chloride with two portions of 20 ml. each of carbon tetrachloride. The aqueous phase was then extracted with two portions of 50 ml. each of ethyl acetate. The combined ethyl acetate extracts were then backwashed using 10 ml. of water and the ethyl acetate removed under vacuum to leave 4.3 g. of pale viscous syrup which crystallized when triturated with water. A sample (1.5 g.) was further purified by dissolution in 25 ml. of ethyl acetate and passing down a small column containing 12 g. of activated silica gel. Some dark material remained at the top of the column whereas the bulk of the material was not adsorbed. Upon removal of the ethyl acetate the material crystallized upon tituration using water. The very pale pink crystals collapsed at 124-5C. and melted at 140 C. Thin layer chromatography showed the product to be homogeneous and the infra red showed a characteristic ester absorption band at 1,735 cm. The compound was optically active [01],, 79 (C, 2.8 ethyl acetate); Analysis calculated for benzyl plicatate C H O C, 63.2%; H, 5.51%. Found: C, 62.67%; H, 5.51%.

The plicatic acid esters of our invention were tested to determine the antioxidant properties or activity of these compounds. The antioxidant activity was evaluated by the standard A.O.C.S. method in which the relative worth of a particular compound is determined by the number of hours it takes for a sample of a given fat or oil containing 0.01 percent by weight of the compound to develop a peroxide value of 100 me per 1,000 gms. of oil or fat. This value of 100 is referred to as the standard of rancidity. Tables I and 11 set forth the relative effectiveness of the esters of our invention, as compared with plicatin, plicatic acid and the pure substrate, as antioxidants for lard and safflower oil, based on the aforementioned standards of rancidity for these substrates.

TABLE I Antioxidant Effectiveness in Lard Time in Hours to Compound Standard rancidity Value (100) n-propyl plicatate I 37.5 I

TABLE I1 Antioxidant Effectiveness in Safi'lower Oil Time in Hours to Compound Standard rancidity Value (100) iso-propyl plicatate 11 n-propyl plicatate 10. n-butyl plicatate 10.5 plicatic acid 10.25 plicatin 9.5 ethyl plicatate 9.5 n-hexyl plicatate 9.25 methyl plicatate 9 dodecyl plicatate 8.75 octadecyl plicatate 8.5 control (pure safflower oil) 6.75

We claim:

1. In the combination of an edible oil or fat and at least one antioxidant therefor, the improvement which comprises utilizing as said antioxidant at least one ester of plicatic acid having the structural formula I where R is an organic radical of the group consisting of alkyl radicals which contain from one to 18 carbon atoms and an aryl radical containing seven carbon atoms.

2. The combination according to claim 1 where R is a methyl radical.

3. The combination according to claim 1 where R is an ethyl radical.

4. The combination according to claim 1 where R is a propyl radical.

5. The combination according to claim 1 where R is a dodecyl radical.

6. The combination according to claim 1 where R is a benzyl radical.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,75%??? Dated August 28, 1973 Inventor(s) John Howard et al.

It is certified that error appears in the above-identified patent and' that said Letters Patent are hereby corrected as shown below:

On the cover sheet, itemEZZI should read as follows:

- Filed August 13, 1971 Signed and sealed this 30th day of April 1971+.

( L) Attest: I

EDWARD T LFLETCHEHJR. C. MARSHALL DANN' Attesting; Officer Commissioner of Patents uscoMM-oc 60376-P69 I t 0,5. GUVERNMENT PRINTING QFFICE 5 5 0-366-33, I

oam 90-1050 (10-59) UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3, 75 1-, 937 Dated August 23, 197} Inventor(s) John Howard et 8.1.

It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

On the cover sheet, itemEZPj should read as follows Filed August 13, 1971 Signed and sealed this 30th day of April 197R.

( L) Attest:

EDWARD T LFLETCHEILJR. C. MARSHALL DANN Commissioner of Patents Attesting Officer USCOMM'DC 6O376-P69 ".5. GOVERNMENT PRINTING O FFICE "II O-lCSfiiSl.

FQRM P0-105O (10-69) 

2. The combination according to claim 1 where R is a methyl radical.
 3. The combination according to claim 1 where R is an ethyl radical.
 4. The combination according to claim 1 where R is a propyl radical.
 5. The combination according to claim 1 where R is a dodecyl radical.
 6. The combination according to claim 1 where R is a benzyl radical. 